The Intricate Relationship between Psychotic-Like Experiences and Associated Subclinical Symptoms in Healthy Individuals

The interplay between subclinical psychotic, negative, and affective symptoms has gained increased attention regarding the etiology of psychosis spectrum and other mental disorders. Importantly, research has tended to not differentiate between different subtypes of psychotic-like experiences (PLE) although they may not have the same significance for mental health. In order to gain information on the subclinical interplay between specific PLE and other symptoms as well as the significance of PLE for mental health, we investigated their specific associations in 206 healthy individuals (20–60 years, 73 females) using correlational and linear regression analyses. PLE were assessed with the Magical Ideation Questionnaire, the revised Exceptional Experiences Questionnaire, and subscales of the Schizotypal Personality Questionnaire (SPQ). The revised Symptom Checklist 90, the SPQ, and the Physical Anhedonia Scale were used to measure subclinical negative symptoms, affective symptoms, and other symptoms such as, emotional instability. As hypothesized, we found that (1) most affective symptoms and all other subclinical symptoms correlated positively with all PLE, whereas we found only partial associations between negative symptoms and PLE. Notably, (2) magical ideation and paranormal beliefs correlated negatively with physical anhedonia. In the regression analyses we found (3) similar patterns of specific positive associations between PLE and other subclinical symptoms: Suspiciousness was a specific predictor of negative-like symptoms, whereas ideas of reference, unusual perceptual experiences, and dissociative anomalous perceptions specifically predicted anxiety symptoms. Interestingly, (4) ideas of reference negatively predicted physical anhedonia. Similarly, paranormal beliefs were negatively associated with constricted affect. Moreover, odd beliefs were a negative predictor of depression, emotional instability, and unspecific symptoms. Our findings indicated that subtypes of PLE are differentially implicated in psychological functioning and should therefore not be categorized homogeneously. Moreover, paranormal beliefs, odd beliefs, and partly ideas of reference might also contribute to subjective well being in healthy individuals. Our results might serve as a starting point for longitudinal studies investigating the interplay of subtypes of subclinical symptoms along a psychopathological trajectory leading to mental disorders. Importantly, this research might help to improve therapeutic strategies for psychosis prevention

Measurement of cerebral oxygen pressure in living mice by two-photon phosphorescence lifetime microscopy

The ability to quantify partial pressure of oxygen (pO2) is of primary importance for studies of metabolic processes in health and disease. Here, we present a protocol for imaging of oxygen distributions in tissue and vasculature of the cerebral cortex of anesthetized and awake mice. We describe in vivo two-photon phosphorescence lifetime microscopy (2PLM) of oxygen using the probe Oxyphor 2P. This minimally invasive protocol outperforms existing approaches in terms of accuracy, resolution, and imaging depth

Capillary micromechanics: Measuring the elasticity of microscopic soft objects

We present a simple method for accessing the elastic properties of microscopic deformable particles. This method is based on measuring the pressure-induced deformation of soft particles as they are forced through a tapered glass microcapillary. It allows us to determine both the compressive and the shear modulus of a deformable object in one single experiment. Measurements on a model system of poly-acrylamide microgel particles exhibit excellent agreement with measurements on bulk gels of identical composition. Our approach is applicable over a wide range of mechanical properties and should thus be a valuable tool for the characterization of a variety of soft and biological materials

Effect of soluble complement receptor type 1 on reperfusion edema and neutrophil migration after lung allotransplantation in swine

AbstractObjective: Soluble complement receptor type 1 inhibits complement activation by blocking C3 and C5 convertases of the classical and alternative pathways. We evaluated the effect of soluble complement receptor type 1 on lung allograft reperfusion injury. Methods: Left lung transplantation was performed in 13 weight-matched pigs (25 to 31 kg) after prolonged preservation (20 hours at 1° C). One hour after reperfusion the recipient contralateral right lung was excluded to assess graft function only. Complement activity and C3a levels were measured after reperfusion and at the end of the assessment. Extravascular lung water index, intrathoracic blood volume, and cardiac output were assessed during a 5-hour observation period. Gas exchange and hemodynamics were monitored. At the end of the 5-hour assessment period, myeloperoxidase assay and bronchoalveolar lavage were performed to assess neutrophil migration, and C5b-9 (membrane attack complex) deposits in the allograft were detected by immunohistochemistry. Two groups were studied. In group II (n = 6) recipient animals were treated with soluble complement receptor type 1 (15 mg/kg) 15 minutes before reperfusion. Group I (n = 7) served as the control group. Results: Serum complement activity was completely inhibited in group II. In contrast to group I, C5b-9 complexes were not detected in group II allograft tissue samples. C3a was reduced to normal levels in group II (p = 0.00005). Extravascular lung water index was higher in group I animals throughout the assessment period (p = 0.035). No significant difference in allograft myeloperoxidase activity (p = 0.10) and polymorphonuclear leukocyte count of the bronchoalveolar lavage fluid (p = 0.057) was detected. Conclusion: Inhibition of the complement system by soluble complement receptor type 1 blocks local complement activation in the allograft and reduces posttransplantation reperfusion edema but does not improve hemodynamic parameters. (J Thorac Cardiovasc Surg 1998;116:90-7

Caffeine Impairs Myocardial Blood Flow Response to Physical Exercise in Patients with Coronary Artery Disease as well as in Age-Matched Controls

BACKGROUND: Caffeine is one of the most widely consumed pharmacologically active substances. Its acute effect on myocardial blood flow is widely unknown. Our aim was to assess the acute effect of caffeine in a dose corresponding to two cups of coffee on myocardial blood flow (MBF) in coronary artery disease (CAD). METHODOLOGY/PRINCIPAL FINDINGS: MBF was measured with (15)O-labelled H2O and Positron Emission Tomography (PET) at rest and after supine bicycle exercise in controls (n = 15, mean age 58+/-13 years) and in CAD patients (n = 15, mean age 61+/-9 years). In the latter, regional MBF was assessed in segments subtended by stenotic and remote coronary arteries. All measurements were repeated fifty minutes after oral caffeine ingestion (200 mg). Myocardial perfusion reserve (MPR) was calculated as ratio of MBF during bicycle stress divided by MBF at rest. Resting MBF was not affected by caffeine in both groups. Exercise-induced MBF response decreased significantly after caffeine in controls (2.26+/-0.56 vs. 2.02+/-0.56, P<0.005), remote (2.40+/-0.70 vs. 1.78+/-0.46, P<0.001) and in stenotic segments (1.90+/-0.41 vs. 1.38+/-0.30, P<0.001). Caffeine decreased MPR significantly by 14% in controls (P<0.05 vs. baseline). In CAD patients MPR decreased by 18% (P<0.05 vs. baseline) in remote and by 25% in stenotic segments (P<0.01 vs. baseline). CONCLUSIONS: We conclude that caffeine impairs exercise-induced hyperaemic MBF response in patients with CAD to a greater degree than age-matched controls

Disruption of Intraflagellar Transport in Adult Mice Leads to Obesity and Slow-Onset Cystic Kidney Disease

SummaryThe assembly of primary cilia is dependant on intraflagellar transport (IFT), which mediates the bidirectional movement of proteins between the base and tip of the cilium. In mice, congenic mutations disrupting genes required for IFT (e.g., Tg737 or the IFT kinesin Kif3a) are embryonic lethal, whereas kidney-specific disruption of IFT results in severe, rapidly progressing cystic pathology [1–3]. Although the function of primary cilia in most tissues is unknown, in the kidney they are mechanosenstive organelles that detect fluid flow through the tubule lumen [4]. The loss of this flow-induced signaling pathway is thought to be a major contributing factor to cyst formation [5–7]. Recent data also suggest that there is a connection between ciliary dysfunction and obesity as evidenced by the discovery that proteins associated with human obesity syndromes such as Alström and Bardet-Biedl localize to this organelle [8]. To more directly assess the importance of cilia in postnatal life, we utilized conditional alleles of two ciliogenic genes (Tg737 and Kif3a) to systemically induce cilia loss in adults. Surprisingly, the cystic kidney pathology in these mutants is dependent on the time at which cilia loss was induced, suggesting that cyst formation is not simply caused by impaired mechanosensation. In addition to the cystic pathology, the conditional cilia mutant mice become obese, are hyperphagic, and have elevated levels of serum insulin, glucose, and leptin. We further defined where in the body cilia are required for normal energy homeostasis by disrupting cilia on neurons throughout the central nervous system and on pro-opiomelanocortin-expressing cells in the hypothalamus, both of which resulted in obesity. These data establish that neuronal cilia function in a pathway regulating satiety responses

Measuring the Influence of Magnetic Vestibular Stimulation on Nystagmus, Self-Motion Perception, and Cognitive Performance in a 7T MRT.

Strong magnetic fields induce dizziness, vertigo, and nystagmus due to Lorentz forces acting on the cupula in the semi-circular canals, an effect called magnetic vestibular stimulation (MVS). In this article, we present an experimental setup in a 7T MRT scanner (MRI scanner) that allows the investigation of the influence of strong magnetic fields on nystagmus as well as perceptual and cognitive responses. The strength of MVS is manipulated by altering the head positions of the participants. The orientation of the participants' semicircular canals with respect to the static magnetic field is assessed by combining a 3D magnetometer and 3D constructive interference in steady-state (3D-CISS) images. This approach allows to account for intra- and inter-individual differences in participants' responses to MVS. In the future, MVS can be useful for clinical research, for example, in the investigation of compensatory processes in vestibular disorders. Furthermore, it could foster insights into the interplay between vestibular information and cognitive processes in terms of spatial cognition and the emergence of self-motion percepts under conflicting sensory information. In fMRI studies, MVS can elicit a possible confounding effect, especially in tasks influenced by vestibular information or in studies comparing vestibular patients with healthy controls

High-Frequency (> 100 GHz) and High-Speed (< 1 ps) Electronic Devices

Contains reports on six research projects and a list of publications.MIT Research Laboratory of Electronics Postdoctoral FellowshipNational Science Foundation Grant DMR 90-22933MIT Lincoln Laboratory Advanced Concept ProgramAdvanced Research Projects Agency Contract MDA972-90-C-0021MIT Lincoln LaboratoryNational Aeronautics and Space Administration Grant NAG2-693U.S. Army Research Office Grant DAAL03-92-G-025